title: Coxsackie and adenovirus receptor is a target and a mediator of estrogen action in breast cancer.
abstract: The involvement of the coxsackie and adenovirus receptor (CAR), an adhesion molecule known to be the main determinant of adenovirus transduction of the cells, in cancer is currently under investigation. Recent reports suggest that CAR levels are elevated in breast cancer, and this may have an impact on its use as means of delivery for gene therapy. In this study, we show that estradiol (E(2)) treatment of the estrogen receptor (ER)-positive breast cancer cell MCF-7 increases CAR levels and, in turn, enhances adenoviral transduction. Employing the transfection of CAR promoters in breast cancer cells, we show that this regulation of CAR expression occurs at the transcriptional level. In addition, and by chromatin immunoprecipitation, we have identified a crucial region of CAR promoter that controls E(2) responsiveness of CAR gene through the recruitment of ER. Moreover, utilizing CAR antibodies or CAR silencing by RNA interference repressed the estrogen-dependent growth of breast cancer cells, whereas the stable expression of CAR in MCF-7 or MDA-MB-231 cells led to an increased proliferation. Altogether, our data suggest that CAR is a novel estrogen-responsive gene, which is involved in the E(2)-dependent proliferation of breast cancer cells.
authors.affiliation: INSERM, U844, Hôpital Saint Eloi, Montpellier F-34091, France.
authors.forename: David
authors.initials: D
authors.lastname: Vindrieux
authors.forename: Ludovic
authors.initials: L
authors.lastname: Le Corre
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.forename: Raphaël
authors.initials: R
authors.lastname: Métivier
authors.forename: Pauline
authors.initials: P
authors.lastname: Escobar
authors.forename: Andrès
authors.initials: A
authors.lastname: Caicedo
authors.forename: Madly
authors.initials: M
authors.lastname: Brigitte
authors.forename: Gwendal
authors.initials: G
authors.lastname: Lazennec
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000260:Adenoviruses, Human / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000235:genetics; D004967:Estrogens / Q000502:physiology*; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D004958:Estradiol